Our research is designed to determine whether target cells for the gonadotropin hormones exist in human/murine melanoma and ovarian cancer and, as such, whether the growth and differentiation of these neoplasms is modulated or dependent on these trophic hormones. The specific aims include: (1)\characterization of available and occupied receptors for luteinizing hormone (LH), chorionic gonadotropin (CG) and for follicle-stimulating hormone (FSH) and assessment of gonadotropin-sensitive adenylyl cyclase activity in surgical biopsies and cultured cell lines of human/murine ovarian tumors and melanomas; (2)\correlation of ectopic gonadotropin production with gonadotropin receptor-adenylyl cyclase activity in tumor samples; and (3)\examination of the effects of gonadotropins on the growth and differentiation of ovarian tumor and melanoma cells in athymic, nude mice. Available and total (available plus occupied) gonadotropin receptors will be characterized from the specific binding of 125I-labeled hLH, hCG and hFSH to particulate preparations of tumor samples before and after acid treatment. Adenylyl cyclase activity will be assessed from the conversion of [alpha 32P] ATP to [alpha 32P] cyclic AMP by tissue/cell homogenates. The presenceof endogenous gonadotropin-like substances in neoplasms will be examined by immunological (radioimmunoassay), biological (radioreceptor assay) and chemical (chromatography) methods. Finally, the effects of LH-CG and FSH on the growth/differentiation of tumor cells will be tested in athymic nude mice. The combined objectives are basic to our understanding of the role of gonadotropin hormones in the etiology and regulation of ovarian cancers and melanoma. The investigation will provide new information on the cellular mechanisms regulating these neoplasms and possibly offer novel methods of therapy of ovarian cancer and melanoma related to the control of gonadotropin secretion and action.